title: Resolution of PMA-induced skin inflammation involves interaction of IFN-γ and ALOX15.
abstract: BACKGROUND
  Acute inflammation and its timely resolution play important roles in the body's responses to the environmental stimulation. Although IFN-γ is well known for the induction of inflammation, its role in the inflammation resolution is still poorly understood.
  
  
  RESULTS
  In this study, we investigated the function of interferon gamma (IFN-γ) during the resolution of PMA-induced skin inflammation in vivo. The results revealed that the expression levels of IL-6, TNF-α, and monocyte chemoattractant protein 1 (MCP-1) in skin decreased during the resolution stage of PMA-induced inflammation, while IFN-γ is still maintained at a relatively high level. Neutralization of endogenous IFN-γ led to accelerated reduction of epidermal thickness and decreased epithelial cell proliferation. Similarly, decreased infiltration of inflammatory cells (Gr1(+) or CD11b(+) cells) and a significant reduction of proinflammatory cytokines were also observed upon the blockade of IFN-γ. Furthermore, neutralization of IFN-γ boosted ALOX15 expression of the skin during inflammation resolution. In accordance, application of lipoxin A4 (LXA4, a product of ALOX15) obtained a proresolution effect similar to neutralization of IFN-γ. These results demonstrated that through upregulating ALOX15-LXA4 pathway, blockage of IFN-γ can promote the resolution of PMA-induced skin inflammation.
authors.affiliation: Research Center for Immunology, Xinxiang Medical University, Xinxiang, Henan 453003, China.
authors.forename: Guojun
authors.initials: G
authors.lastname: Zhang
authors.forename: Xiaoman
authors.initials: X
authors.lastname: Liu
authors.forename: Chunhui
authors.initials: C
authors.lastname: Wang
authors.forename: Liwei
authors.initials: L
authors.lastname: Qu
authors.forename: Jingjing
authors.initials: J
authors.lastname: Deng
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Zhihai
authors.initials: Z
authors.lastname: Qin
mesh_terms: D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism*; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D007249:Inflammation / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism*; D044045:Lipoxins / Q000627:therapeutic use; D008297:Male; D051379:Mice; D060888:Real-Time Polymerase Chain Reaction; D012867:Skin / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*
chemical_list: D044045:Lipoxins; C040527:lipoxin A4; D007371:Interferon-gamma; C521960:Alox15 protein, mouse; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase; D013755:Tetradecanoylphorbol Acetate